Autoimmune diseases are those immune system disorders characterized by production of antibodies that react with antigens of the patient's own tissues. More than 30 autoimmune diseases are presently known; these include many which have received much public attention, including rheumatoid arthritis, multiple sclerosis and systemic lupus erythematosus (SLE). The production of specific autoantibodies is associated with certain autoimmune diseases. For a description of the immune mechanisms and autoantibodies involved in autoimmune disease, See Schwartz, R. S., et al. in Fundamental Immunology, Second Edition, Paul, W. E., editor, Raven Press, New York (1989) pp. 819-866, incorporated herein by reference.
Autoimmune diseases can be categorized into organ-specific diseases and systemic diseases. Organ-specific autoimmune diseases affect a single organ, such as the thyroid gland, or a physiological system, such as the neuromuscular system. The autoantigens involved in organ-specific diseases are primarily antigens specific to an organ and may be implicated in the pathology of the disease. For example, autoantibodies to thyroglobulin are observed in autoimmune thyroiditis and appear to be involved in the pathology of the disease. Systemic autoimmune diseases, on the other hand, affect multiple physiological systems. The autoantibodies involved in systemic autoimmune disease are generally reactive with more ubiquitous autoantigens, including a group of antigens found in the nucleus of cells. These latter group of autoantigens include DNA, histones, and a number of ribonucleoproteins. See Schwartz, R. S., et al., supra.
Detection and measurement of autoantibodies is used to diagnose and monitor a number of autoimmune diseases. For example, autoantibodies reactive with nuclear autoantigens are generally measured in the clinical laboratory in the antinuclear antibody (ANA) test. The ANA test is an indirect immunofluorescence test that uses a cell line or tissue section as a source for nuclear autoantigens. Nuclear fluorescence in the ANA test indicates the presence of nuclear autoantibodies. Furthermore, the pattern of fluorescence observed can be correlated with the presence of autoantibodies reactive with specific nuclear antigens.
The ANA test is widely used to detect autoantibodies to nuclear antigens, and is useful in the diagnosis of several systemic autoimmune diseases. However, there are problems associated with the ANA test which limit its diagnostic usefulness. In particular, it is difficult to find cell lines or tissue sources that have sufficiently high amounts of all of the desired nuclear autoantigens. Some nuclear autoantigens are produced at only low levels in cell lines and tissue sources commonly used for ANA testing.
An example of such a nuclear autoantigen is Ro/SS-A. Autoantibodies to Ro/SS-A are associated with SLE, neonatal lupus erythematosus, Sjogren's syndrome and other rheumatic diseases. Measurement of anti-Ro/SS-A autoantibodies is important in the diagnosis of these disorders. Therefore, cell lines that express higher levels of Ro/SS-A or other autoantigens which are normally present in low amounts are needed. For nuclear autoantigens such as Ro/SS-A, it would be particularly useful if a cell line also expressing other autonuclear antigens can be modified to overexpress Ro/SS-A, so that the cell line can be used for an improved ANA test.